A new perspective during laryngo-tracheal surgery: the use of an ultra-thin endotracheal tube (Tritube®) and flow-controlled ventilation—a retrospective case series and a review of the literature

Background Upper airway surgery often poses a challenge to both anesthesiologists and surgeons, as airway access, mechanical ventilation, and surgical difficulties may occur in a tricky combination. To fulfill the need for a tubeless surgery, techniques such as apneic oxygenation or jet ventilation may be used, which carry the risk of several complications. The ultrathin cuffed endotracheal tube Tritube can be used with flow-controlled ventilation (FCV) to provide adequate surgical field and ventilation. To assess the feasibility, safety, and effectiveness of this technique, we describe a series of 21 patients, with various lung conditions, undergoing laryngo-tracheal surgery with FCV delivered via Tritube. Moreover, we perform a narrative systematic review to summarize clinical data on the use of Tritube during upper airway surgery. Results All patients were successfully intubated in one attempt with Tritube. The median (interquartile range [IQR]) tidal volume was 6.7 (6.2–7.1) mL/kg of ideal body weight, the median end-expiratory pressure was 5.3 (5.0–6.4) cmH2O, and the median peak tracheal pressure was 16 (15–18) cmH2O. The median minute volume was 5.3 (5.0–6.4) L/min. Median global alveolar driving pressure was 8 (7–9) cmH2O. The median maximum level of end-tidal CO2 was 39 (35–41) mmHg. During procedures involving laser, the maximum fraction of inspired oxygen was 0.3, with the median lowest peripheral oxygen saturation of 96% (94–96%). No complications associated with intubation or extubation occurred. In one patient, the ventilator needed to be rebooted for a software issue. In two (10%) patients, Tritube needed to be flushed with saline to remove secretions. In all patients, optimal visualization and accessibility of the surgical site were obtained, according to the surgeon in charge. Thirteen studies (seven case reports, two case series, three prospective observational studies, and one randomized controlled trial) were included in the narrative systematic review and described. Conclusions Tritube in combination with FCV provided adequate surgical exposure and ventilation in patients undergoing laryngo-tracheal surgery. While training and experience with this new method is needed, FCV delivered with Tritube may represent an ideal approach that benefits surgeons, anesthesiologists, and patients with difficult airways and compromised lung mechanics.


Background
The selection of appropriate strategies for managing the airway remains a challenge in patients requiring upper airway surgery. The need to provide adequate oxygenation and carbon dioxide (CO 2 ) removal in a secured airway may conflict with the demand for a clean, clear, and spacious surgical field. Moreover, patients undergoing laryngo-tracheal surgery may suffer from increased airway resistance and/or respiratory system elastance, which can require prioritizing adequate ventilation over-optimized surgical conditions. Several techniques for airway management during laryngo-tracheal surgery, e.g., microlaryngeal tubes (MLTs) and high-frequency jet ventilation (HFJV), have been developed, all providing certain advantages, as well as disadvantages [1,2].
MLTs are endotracheal tubes with an inner diameter (ID) of 5.0-6.0 mm. Still, in cases of severe tracheal stenosis, the placement of such tubes may be traumatic or even impossible. Furthermore, expiration times might need to be prolonged to avoid overinflation of the lungs, potentially compromising the adequacy of gas exchange, particularly in patients with increased airway resistance and/or respiratory system elastance [3].
HFJV requires the insufflation of oxygen under high pressures through a thin catheter. Exhalation relies on the passive egress of gas and thus demands a patent airway. A "tubeless" HFJV method, i.e., supraglottic superimposed HFJV (SSHFJV), was introduced in the late 90s [4]. Then, surgery is performed through a laryngoscope with integrated jet stream nozzles, enabling ventilation without the need for tracheal intubation. Being supraglottic and tubeless, SSHFJV reduces the risk of barotrauma and fire in case of laser surgery [5,6]. However, the airway needs to be open to allow a passive egress of gases and to avoid barotrauma. The open airway always carries a risk of aspiration. The jet stream and significant backflow of gases may cause movement of anatomical structures and may generate an aerosol spread [5]. Also, in patients with compromised lung mechanics, SSHFJV may fail because of inadequate ventilation [7].
In situations where the introduction of any tube or catheter would impede the surgical procedure, fully tubeless techniques have been developed. These include the use of HFJV with intermittent phases of apnea, as well as apneic oxygenation with the application of high-flow oxygen [8,9]. Yet, these methods may result in significant hypercarbia and do not suit those patients with limited apneic window, such as the morbidly obese.
In sum, airway management of upper airway surgical patients with the aforementioned methods may often require the acceptance of suboptimal ventilation and/or compromised surgical conditions.
The most recent innovation in the field is an ultrathin cuffed endotracheal tube (Tritube ® , Ventinova Medical, Eindhoven, the Netherlands), with an ID of 2.3 mm and an outer diameter (OD) of 4.4 mm, that increases surgical exposure, while sealing the airway [10,11] (Fig. 1). Because of the combination of a cuff sealing the airway and a narrow ID, passive expiration is not possible: the high resistant circuit prevents abrupt and passive deflation of the lungs after inspiration. Therefore, the use of Tritube requires expiration to be actively generated through suctioning. Manual ventilator Ventrain and mechanical ventilator Evone (both Ventinova Medical BV, Eindhoven, the Netherlands) [12][13][14][15] provide active expiration by flow-controlled ventilation (FCV). FCV is a ventilatory mode where both inspiratory and expiratory flow rates are maintained constant and low, i.e., < 20 L/min, throughout the respiratory cycle by regulating tracheal pressure, as measured through a dedicated lumen opening at the distal end of the endotracheal tube. Therefore, intratracheal pressure linearly increases and decreases between the chosen end-expiratory pressure (EEP) and peak pressure. During FCV, the inspiratory flow rate, inspiratory to expiratory (I:E) ratio, peak inspiratory pressure, EEP, and FiO 2 are set by the user, whereas tidal volume and respiratory rate vary depending on ventilator settings and the mechanical properties of the patient's respiratory system (Fig. 2). Moreover, thanks to accurate mass flow controllers, FCV allows titrating ventilation settings based on measured respiratory system mechanics [16,17]. The differences between FCV and conventional mechanical modes, i.e., volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV), regarding the gas flow, tidal volume, and airway pressure waveforms are illustrated in Fig. 3.
We present a retrospective series of 21 patients undergoing laryngo-tracheal surgery with FCV delivered by Tritube. We hypothesize that FCV in combination with Tritube guarantees adequate airway management, surgical exposure, and gas exchange. Also, we perform a narrative systematic review to summarize clinical data on the use of Tritube during upper airway surgery.

Patient characteristics
Twenty-one patients with median (interquartile range [IQR]) age of 69 (62-73) years and median American Society of Anesthesiologists (ASA) score of 2 (2-3) are Using FCV requires the setting of four parameters: (1) inspiration flow, (2) I:E ratio, (3) peak pressure, and (4) end-expiratory pressure (EEP). At the set flow rate, gas is insufflated from set EEP until it reaches the set peak pressure. Then, the flow is reversed and gas is sucked out at the rate to reach the set I:E ratio until EEP is reached, aiming for a linear decrease in intratracheal pressure. Then, a next insufflation with the set inspiration flow is started. Applied tidal volume results from the set driving pressure and respiratory system compliance  Table 1. Surgical procedures were transoral laser microsurgery (TLM) (n=8), cordectomy (n=9), microlaryngoscopy for laryngeal bioexeresis (n=1), scar toilet after laryngeal TLM (n=1), exeresis of glottic synechia (n=1), and endoscopic supraglottic laryngectomy (n=1). Four (19%) patients had developed severe subglottic/supraglottic stenoses prior to surgery (Fig. 4).

Airway management
Upon establishment of total intravenous anesthesia (TIVA) (see the "Methods" section), all patients were successfully intubated in one attempt with Tritube by means of videolaryngoscopy. No complications associated with intubation, intraoperative ventilation, or extubation occurred. In two (10%) patients, Tritube needed to be flushed with saline to remove secretions. In all patients, optimal visualization and accessibility of the surgical site were obtained, according to the surgeon in charge. In one case, the adjustments of ventilator settings were suddenly disabled during surgery, despite regularly continuing ventilation, requiring a system reboot. We contacted the manufacturer and the issue was solved in the currently available software.

Narrative systematic review
After applying the selection criteria (see the "Methods" section), 38 studies were initially identified in PubMed and 19 in ResearchGate. After removing duplicates and applying the exclusion and eligibility criteria, 13 studies were included in the systematic review ( Fig. 5): seven case reports, two case series, three prospective observational studies, and one randomized controlled trial (RCT) were selected. Table 3 summarizes these publications.
The first clinical cases were published in 2018, describing the use of Tritube and Evone in difficult airways and including the use of Tritube for awake intubation [31,32]. Then, the first prospective observational study reported   easy intubation and adequate ventilation in patients undergoing ENT surgery without difficult airway [30]. A direct comparison between Tritube and 6.0-mm-ID MLTs in a randomized controlled trial (RCT), including 40 patients without a difficult airway undergoing elective laryngeal surgery, showed the use of Tritube, as compared to VCV, to result in significantly less concealment of laryngeal structures, improved surgical conditions for less experienced surgeons, better lung aeration, and increased respiratory system compliance [29].
Observational studies including patients with difficult airway showed that Tritube establishes optimal working conditions from laryngeal surgeons' perspective [28]. It can overcome the drawbacks of jet ventilation, reducing aspiration and contamination risks, while providing adequate ventilation with FCV [20,28]. Kuut and colleagues showed that, in most cases of tracheal resection, Tritube can avoid the need for cumbersome cross-field intubations [19]. The small OD of Tritube allows stitching the tracheal anastomosis, while keeping the tube in situ and providing continuous ventilation in a sealed airway. Further, Tritube provided good conditions for the visual assessment of the anastomosis and laryngeal edema after surgery.
In total, data on 75 patients ventilated through Tritube were reported in 13 publications. In five publications, adverse events occurred. Tube obstruction was the most frequently reported event, which happened 16 times in eight patients (of which six undergoing tracheal resection). Obstruction was caused by surgical manipulation (six times), secretions (seven times), kinking outside of the patient (once), or unknown reasons (twice). In all cases, secretions could be removed by flushing the lumens with saline. Tube dislocation was reported six times and was due to surgical manipulation (three times) or coughing (three times). Dislocation by coughing was only reported in the early studies. Tritube's relatively big cuff, due to its small lumen, and the high resistant breathing circuit generate the risk for dislodgement upon coughing. These publications likely made users more aware of the importance of optimizing the depth of anesthesia in order to avoid coughing and spontaneous breathing efforts. Cuff damage was reported only once, upon surgical manipulations. Tritube had to be replaced, which went uneventful. In two cases, the Evone ventilator caused ventilation difficulties. In both cases, a software update solved the issue [21,29].
No direct clinical comparisons between SSHFJV and FCV were published.

Discussion
In this series of 21 patients with various lung comorbidities undergoing laryngo-tracheal surgery for different indications, we show that Tritube in combination with FCV provides good surgical conditions and adequate gas exchange at relatively low minute volumes and global alveolar driving pressures. Our results are in line with earlier publications and suggest this technique  Case report Tracheal resection due to severe stenosis after being ventilated due to COVID-19-related ARDS.   to be feasible even in patients with compromised lung mechanics. Current strategies for airway management during upper airway surgery often require the acceptance of risks related to anesthetic and/or surgical considerations. In contrast, the use of FCV delivered by Tritube may preserve surgical view, while allowing airway protection and adequate gas exchange. First, in our patients, the small OD of Tritube (4.4 mm) allowed easy intubation, even in case of tracheal stenosis, and a spacious working field for the surgeon. Second, no aspiration event occurred, thus minimizing the risk of aspiration pneumonia and atelectasis and aiding in achieving a clean surgical environment. Third, no passive backflow of gases occurred, hence reducing aerosol spread and improved surgical view. This last advantage was recognized by experts in the field of airway management, who recently published recommendations aiming at minimizing the risk of aerosol spread in the setting of upper airway surgery during the COVID-19 pandemic [2]. Furthermore, according to the recent description of surgical tracheotomy using Tritube and FCV, these techniques could increase the safety of patients and medical personnel by avoiding the need for cumbersome cross-field intubations and reducing the aerosol generation, respectively [33]. Fourth, Tritube may be less rigid and traumatic than laserresistant tubes. While laser resistance is not claimed for Tritube by the manufacturer, we did use it during laser surgery by protecting the cuff with saline-soaked gauze as described earlier [20,28], which, being located distally to the lesion, did not compromise the surgical exposure. The FiO 2 could be easily reduced to 0.3 or lower in our patients.
The practical advantages of Tritube with respect to airway management and surgical conditions are combined with several ventilation benefits.
Second, since Tritube enables intratracheal pressure measurements and Evone utilizes mass flow controllers, respiratory system mechanics can be precisely determined [41,42]. This offers the possibility to individually titrate applied flow and pressure based on the dynamic compliance of the patient's respiratory system [16,43]. This approach might reduce driving pressure, i.e., the difference between plateau pressure and positive endexpiratory pressure and mechanical power, i.e., the total energy transferred from the mechanical ventilator to the lungs during inflation [17,42]. In our study, we observed adequate gas exchange and acceptable driving pressures in all patients, except for a post-COVID-19 patient (patient #3) with severely impaired respiratory system mechanics. In this patient, a very high global alveolar driving pressure (23 cmH 2 O) was required to achieve acceptable oxygenation and normocapnia, while using a minute volume of only 7.4 L/min. In a patient with COVID-19 acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU), Spraider et al. recently found FCV to improve oxygenation, as compared to PCV, while reducing the applied energy of ventilation [43]. Recently, in a small crossover study in 10 patients with COVID-19 ARDS, our group found lower mechanical power and higher ventilation efficiency during FCV compared to VCV [44]. Another recent crossover study comparing FCV with VCV also observed improved ventilation efficiency by FCV [45].
Our study has some limitations. First, the small sample size of our retrospective single-center case series makes our findings exploratory and hypothesis-generating. Importantly, we did not compare FCV delivered by Tritube with other airway management strategies in our patients. Further prospective comparative studies with larger sample sizes are needed to confirm our findings. Second, the achievement of adequate gas exchange could not be confirmed by arterial blood gas analyses, as invasive arterial pressure was not part of our routine intraoperative monitoring. Third, no quantitative assessment of surgical exposure was reported nor imaging aiming at evaluating lung aeration was performed. Fourth, this series of cases was performed by one anesthesiologist (AG), who has 15 years of experience, of which many in airway surgery procedures. The determination of a learning curve was out of scope of this study. Though, in order to gain adequate confidence with the technique, we suggest a minimum of 10 supervised operations.
Some limitations pertaining to FCV and Tritube should also be addressed.
First, FCV represents a novel ventilator mode, requiring specific training.
Second, training is also recommended for the management of Tritube. The small ID of Tritube makes it more susceptible to obstruction by secretions, which may affect or even interrupt ventilation. Therefore, a "plan B" (e.g., hand-held ventilator Ventrain) is always needed, but proper preparation on the forehand can significantly reduce the risk on obstructions. First, it is important to judge on the probability of secretions (e.g., COPD, secretion retention due to obstruction) and to remove these where possible by asking the patient to cough before anesthetizing and to suck away secretions before intubation. Others described to administer glycopyrronium to reduce mucosal secretions [28]. During intubation, Tritube is advanced from its stylet further down the trachea while turning. When the tube is at the right position, it should be slightly pulled back before inflating the cuff to free Tritube's tip from the tracheal wall. Then, one can flush both the ventilation lumen and pressure lumen with air to ensure the absence of any obstructions. Upon starting FCV ventilation, the machine will also perform a purge with air automatically. During ventilation, irregular pressure curves may indicate the presence of secretions (but may also result from light anesthesia or mispositioning of Tritube). An altered shape of the pressure curve without any other explanation may be solved by flushing the pressure and ventilation lumens using 2-5 cc of saline followed by 15 cc of air. Should the issue persist, one may consider to use the suction catheter to remove secretions from the ventilation lumen after deflating the cuff should be deflated. As mentioned, a mispositioning of Tritube may also affect the shape of the pressure curve. The tube is 45 cm long and may touch the carina or migrate into a bronchus because of surgical manipulations. Furthermore, the higher flexibility of Tritube, when compared to reinforced laser-resistant tubes, makes it more prone to compression during suspension laryngoscopy. Complete obstruction of one of the lumens will be detected by the ventilator, that responds by alarming while purging the lumens. Also, one may use the Jet ventilation mode to purge away an obstruction with a deflated cuff. Third, as mentioned earlier, Tritube is not laser-safe and its use during laser surgery is not intended by the manufacturer. Indeed, we report the Tritube's cuff damage during one case. However, given its small OD and the resulting unimpeded surgical view, no complications during laser surgery have been reported by other authors, provided that FiO 2 is lowered and the tube and/or its cuff are covered with a wet gauze [20,28].
Fourth, patients ventilated with FCV should be kept under TIVA with muscle relaxation throughout the procedure to avoid spontaneous breathing efforts and coughing, which may lead to Tritube dislocation and interruption of ventilation [30].

Conclusion
In 21 patients undergoing laryngo-tracheal surgery, we observed that the utilization of the ultrathin and cuffed Tritube in combination with FCV allowed easy intubation, good surgical exposure, low chance of aerosol spread, and adequate gas exchange. Like any other new technique, this method requires device-specific training to get adequate confidence. Our observations add to the growing body of evidence that Tritube and FCV may represent valuable strategies for airway management in laryngo-tracheal surgery, even in patients with lung comorbidities (e.g., post-COVID-19, COPD) and severe tracheal stenosis.

Aim, design, and setting
This study is a single-center retrospective observational study. Twenty-one consecutive patients scheduled for laryngo-tracheal surgery were included between November 2020 and June 2021.
The decision to use Evone and Tritube (both Ventinova Medical BV, Eindhoven, the Netherlands) was made by the anesthesiologist and surgeon in charge based on the indication for treatment. The study was approved by the Local Ethical Committee (Comitato Etico di Sperimentazione Clinica ULSS 2 Marca Trevigiana, Prot. 96489, 19/05/2022) and was conducted in accordance with the principles of the Helsinki Declaration.

Anesthesia
Following adequate pre-oxygenation, TIVA was induced with intravenous propofol and remifentanil, targeting a bispectral index of 40-60 during surgery. Upon induction, patients received fentanyl 2 μg/kg and rocuronium 0.6 mg/kg for neuromuscular blockade with target trainof-four (TOF) of 0 to 1. For decurarization, sugammadex 2 mg/kg was administered based on TOF to minimize the time frame between the initial triggering of the patient and spontaneous breathing allowing extubation.

Intubation and extubation
Tritube is a cuffed endotracheal tube made of polyurethane (length 45 cm, OD 4.4 mm) and has three lumens: a ventilation lumen conducting inspiratory and expiratory gas flow, a pressure measurement lumen allowing measurements of intratracheal pressures, and a cuff lumen to inflate and deflate the low pressure/high volume cuff (Fig. 1).
Tritube was positioned using videolaryngoscopy (C-MAC, Karl Storz Endoskope ® , Tuttlingen, Germany) and gently rotated while directed through the vocal cords. We believe that the rotation of the tip of the tube is particularly important in the case of subglottic stenosis. Since the cuff of the tube is relatively large as compared to its OD, it may compromise the view during intubation. Therefore, the cuff was wrapped around the tube before intubation, which was done by simultaneously rotating the tube covered with a gauze while deflating the cuff.
Upon any occurring obstruction of Tritube, e.g., by secretions, the ventilation and pressure lumens were flushed with saline and/or air.
In patients scheduled for laser-assisted treatment, adequate precautions were taken to avoid damage of Tritube and/or its cuff and to reduce the risk of airway fires. The applied FiO 2 was reduced to 0.3, while the cuff of Tritube was covered with wet gauze (cotonoid strip). As soon as the patient showed the first signs of triggering, the cuff of Tritube was deflated immediately and oxygen insufflation through Tritube was maintained until the patient was ready for extubation.

Ventilation
Upon establishment of TIVA and intubation, Tritube was connected to mechanical ventilator Evone, and FCV was initiated at default settings. Then EEP and peak pressure were optimized based on measured lung mechanics as described below, while keeping the tidal volume around 6 mL/kg of IBW. The inspiratory flow was adjusted to achieve a minute ventilation allowing normal etCO 2 .

FCV setting optimization
Individualization of FCV was based on a previously described method [16]. EEP was stepwise increased or decreased while keeping the driving pressure constant until the highest tidal volume/ compliance was reached. Then, peak pressure was stepwise increased or decreased until the highest compliance was reached, while keeping the tidal volume around 6 mL/kg of IBW.
Finally, the inspiratory flow was adjusted to achieve normocapnia at an I:E ratio of 1:1, which is considered the best for minimizing dissipated energy [17].

Dynamic FCV and global alveolar driving pressure
During FCV, because of the patient's airway resistance, tracheal pressures measured and displayed by the ventilator deviate to a certain extent from the actual alveolar pressures [41]. As a result, the global alveolar driving pressure is typically lower than the tracheal driving pressure calculated from measured intratracheal EEP and peak values, while the calculated dynamic compliance is underestimated [18]. The extent of these deviations is both flow-and resistance-dependent: the higher the set flow and the airway resistance during FCV, the greater the difference between tracheal and global alveolar driving pressures. As the difference in pressures is stable during the entire ventilation cycle, accurate calculations of alveolar driving pressure can be easily performed based on given flow and measured airway resistance [18]. First, the pressure needed to overcome the total resistance (mbar) is calculated by dividing the measured total resistance (mbar/L/s) by the set inspiratory low (L/s). Then, based on the measured dynamic intratracheal peak pressure (mbar) and EEP (mbar), the mean global alveolar pressures can be calculated, as follows: mean global alveolar peak pressure (mbar) = dynamic intratracheal peak pressure (mbar) − pressure needed to overcome resistance (mbar); mean global alveolar EEP (mbar) = dynamic intratracheal EEP (mbar) + pressure needed to overcome resistance (mbar). These calculations assume an I:E ratio of 1.0:1.0, leading to similar flows during inspiration and expiration, and that the resistance measured at peak pressure is similar to that measured at EEP. For convenience, the manufacturer provided a tool to easily perform these calculations and provided a table with pre-calculated values for a quick estimation (Table 4)

Surgery
Various surgical upper airway procedures were performed, using a rigid laryngoscope in all cases. Most of the procedures (20/21) used the operating microscope Leica F40 (Leica Microsystems Srl, Milan, Italy) and the CO 2 laser Lumenis Ultra PulseDuo (Boston Scientific, Marlborough, MA, USA).

Clinical data collection
Data were retrospectively retrieved from the electronic medical files. For all patients, a review of relevant medical history and anesthesia and surgical reports was performed. Twenty parameters (age, gender, body mass index, ASA Physical Status Classification system, duration of ventilation, duration of surgery, surgical procedure, tidal volume, respiratory rate, peak pressure, EEP, inspiratory flow, minute volume, airway resistance, dynamic respiratory system compliance, global alveolar driving pressure [18], FiO 2 , highest etCO 2 , lowest SpO 2 , and complications related to the use of Tritube and Evone) were collected.

Systematic narrative review
We searched PubMed since inception until July 29, 2022, using the following text words: "tritube" OR "flow controlled ventilation" OR ("narrow bore lumen" AND "mechanical ventilation"). Then, we searched Research-Gate using the text word "tritube". All duplicates and irrelevant publications were removed. The following eligibility criteria were applied: (1)